Effects zoledronic acid on bone remodeling in ovariectomized rats: clinical, densiometric and biochemical microtomography

The objective of this study was to prospectively investigate the clinical, densitometric, biomechanical and microtomographyc effects of zoledronic acid in the femurs of 80 female Wistar rats (Rattus norvegicus albinus), with osteoporosis due to bilateral oophorectomy. With the age of thirty days, the animals were randomized into two groups, according to the surgical procedures: bilateral oophorectomy (group O) (n=40) and sham surgery (group S) (n=40). On the 30th postoperative day, the subjects were randomly divided into four groups, according to the intraperitoneal administration of 0.1 mg/kg of zoledronic acid or distilled water: group OAZ (ovariectomized group with zoledronic acid) (n=20), group OAD (ovariectomized group with distilled water) (n=20), group SAZ (sham group with zoledronic acid) (n=20) and group SAD (sham group with distilled water) (n=20). All animals were monthly weighted. The animals were euthanized with a lethal intraperitoneal dose of sodium pentobarbital 3% (80 mg/kg) after a follow up period of nine months (n=40) and 12 months (n=40). For the analysis of weight, it was considered the weight curve throughout the experiment. The right femurs were used for biomechanical tests, analyzing the maximum load (N), the yield point (N) and stiffness coefficient (N/mm). The left femurs were used for both, densitometric (mmAl) and microtomographyc tests, getting the bone volume (mm3), the trabecular number (mm-3), the trabecular diameter (mm) and intertrabecular separation (mm). The statistical analysis was performed through the analysis of variances and complemented with the multiple averages comparison tests, for a 2 x 2 x 2 factorial project (two substances, two types of surgical procedures and two periods of euthanasia). It was used an entirely casual model, with a significance level of 95%. Through the results it was concluded that the zoledronic acid had no influence on the weight of the animals. In the biomechanical evaluation, zoledronic acid significantly increased the maximum load and yield point, decreasing the stiffness coefficient of the bones. Concerning to the densitometric analysis, the zoledronic acid significantly increased the density of the femurs. Concerning to the microtomographic evaluation, zoledronic acid significantly increased the bone volume, the trabecular number and the trabecular width, reducing, in a significant way, the intertrabecular separation.